title: The NF-kappaB inhibitor SC75741 protects mice against highly pathogenic avian influenza A virus.
abstract: The appearance of pandemic H1N1 and highly pathogenic avian H5N1 viruses in humans as well as the emergence of seasonal H1N1 variants resistant against neuraminidase inhibitors highlight the urgent need for new and amply available antiviral drugs. We and others have demonstrated that influenza virus misuses the cellular IKK/NF-kappaB signaling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention. Here, we show that the novel NF-kappaB inhibitor SC75741 significantly protects mice against infection with highly pathogenic avian influenza A viruses of the H5N1 and H7N7 subtypes. Treatment was efficient when SC75741 was given intravenously in a concentration of 5mg/kg/day. In addition, application of SC75741 via the intraperitoneal route resulted in a high bioavailability and was also efficient against influenza when given 15 mg/kg/day or 7.5 mg/kg/twice a day. Protection was achieved when SC75741 was given for seven consecutive days either prior to infection or as late as four days after infection. SC75741 treatment showed no adverse effects in the concentrations required to protect mice against influenza virus infection. Although more pre-clinical studies are needed SC75741 might be a promising candidate for a novel antiviral drug against influenza viruses that targets the host cell rather than the virus itself.
authors.affiliation: Interfaculty Institute for Cell Biology, Department of Immunology, Eberhard Karls University Tuebingen, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Haasbach
authors.forename: Sarah Julia
authors.initials: SJ
authors.lastname: Reiling
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Karoline
authors.initials: K
authors.lastname: Droebner
authors.forename: Andrea
authors.initials: A
authors.lastname: Rückle
authors.forename: Eike R
authors.initials: ER
authors.lastname: Hrincius
authors.forename: Johann
authors.initials: J
authors.lastname: Leban
authors.forename: Stefan
authors.initials: S
authors.lastname: Strobl
authors.forename: Daniel
authors.initials: D
authors.lastname: Vitt
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.forename: Oliver
authors.initials: O
authors.lastname: Planz
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D001717:Birds; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D053126:Influenza A Virus, H7N7 Subtype / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014774:Virulence
chemical_list: D000998:Antiviral Agents; D016328:NF-kappa B
keywords: Antiviral; Influenza A virus; NF-kappaB inhibitor; SC75741